This proposal is a request for a Leica LMD7000 laser capture microdissection system. This instrument allows for the isolation of single cells or small groups of cells from thin sections of frozen or formalin-fixed paraffin-embedded archival tissue, with the purpose of collecting RNA, DNA or proteins. It enables the investigator to analyze a specific cell population out of a complex tissue environment, with applications including DNA genotyping, RNA transcript profiling, proteomics and signal transduction analysis. This proposal features highly clinically relevant projects from 15 NIH-supported scientists. These projects include a number of studies that focus on the role of cytokines and the endothelium in the control of sepsis, several cancer/hyperplasia-related studies on HPV-induced respiratory papillomas, chronic lymphocytic leukemia, brain tumors and other tumors, the regulation of the blood-brain barrier, pulmonary hypertension, glomerulosclerosis and alcohol addiction. A more basic study on B cell differentiation is also included. Thus, the acquisition of the LCM microscope will significantly enhance the outcomes of over 18 NIH-funded grants. Moreover, the LCM technology should contribute significantly to the long-range research goal of The Feinstein Institute: the translation of the understanding of biological mechanisms to novel treatments and diagnostics. In addition, it will strengthen and expand existing collaborations between the Feinstein Institute and the various clinical departments of the North Shore-Long Island Jewish Health System and maximize the use of its Tissue Donation Program. The LCM system will be housed in the Light Microscopy Core Facility (LMCF) of the Feinstein Institute. Maintenance of the instrument and technical guidance and training of investigators will be supported by the current management of the LMCF. The PI of this application, who also is the LMCF supervisor, in conjunction with the Light Microscopy and Core Services Advisory Committees, will oversee the utilization of the LCM system. LCM-based efforts will be further supported by a pathologist at the North Shore University Hospital, who serves as a consultant, in addition to a number of other collaborating pathologists. A financial plan is in place to recover maintenance costs. Utilization of the LCM system by NIH-funded investigators will be prioritized and efforts will be made to introduce LCM technology and its application to new investigators.